{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T06:21:14Z","timestamp":1777875674631,"version":"3.51.4"},"reference-count":78,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>In numerous studies based predominantly on rodent models, administration of 3,5-diiodo-L-thyronine (3,5-T2), a metabolite of the thyroid hormones (TH) thyroxine (T4) and triiodo-L-thyronine (T3), was reported to cause beneficial health effects, including reversal of steatohepatosis and prevention of insulin resistance, in most instances without adverse thyrotoxic side effects. However, the empirical evidence concerning the physiological relevance of endogenously produced 3,5-T2 in humans is comparatively poor. Therefore, to improve the understanding of 3,5-T2-related metabolic processes, we performed a comprehensive metabolomic study relating serum 3,5-T2 concentrations to plasma and urine metabolite levels within a large general population sample.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Serum 3,5-T2 concentrations were determined for 856 participants of the population-based Study of Health in Pomerania-TREND (SHIP-TREND). Plasma and urine metabolome data were generated using mass spectrometry and nuclear magnetic resonance spectroscopy, allowing quantification of 613 and 578 metabolites in plasma and urine, respectively. To detect thyroid function-independent significant 3,5-T2\u2014metabolite associations, linear regression analyses controlling for major confounders, including thyrotropin and free T4, were performed. The same analyses were carried out using a sample of 16 male healthy volunteers treated for 8 weeks with 250\u2009\u03bcg\/day levothyroxine to induce thyrotoxicosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The specific molecular fingerprint of 3,5-T2 comprised 15 and 73 significantly associated metabolites in plasma and urine, respectively. Serum 3,5-T2 concentrations were neither associated with classical thyroid function parameters nor altered during experimental thyrotoxicosis. Strikingly, many metabolites related to coffee metabolism, including caffeine and paraxanthine, formed the clearest positively associated molecular signature. Importantly, these associations were replicated in the experimental human thyrotoxicosis model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The molecular fingerprint of 3,5-T2 demonstrates a clear and strong positive association of the serum levels of this TH metabolite with plasma levels of compounds indicating coffee consumption, therefore pointing to the liver as an organ, the metabolism of which is strongly affected by coffee. Furthermore, 3,5-T2 serum concentrations were found not to be directly TH dependent. Considering the beneficial health effects of 3,5-T2 administration observed in animal models and those of coffee consumption demonstrated in large epidemiological studies, one might speculate that coffee-stimulated hepatic 3,5-T2 production or accumulation represents an important molecular link in this connection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2018.0549","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T07:37:03Z","timestamp":1569915423000},"page":"1743-1754","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["A Thyroid Hormone-Independent Molecular Fingerprint of 3,5-Diiodothyronine Suggests a Strong Relationship with Coffee Metabolism in Humans"],"prefix":"10.1177","volume":"29","author":[{"given":"Maik","family":"Pietzner","sequence":"first","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany."},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany."},{"name":"MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josef","family":"K\u00f6hrle","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Endokrinologie, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ina","family":"Lehmphul","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Endokrinologie, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Budde","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany."},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabi","family":"Kastenm\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum M\u00fcnchen, Neuherberg, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Brabant","sequence":"additional","affiliation":[{"name":"Medical Clinic I, University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry","family":"V\u00f6lzke","sequence":"additional","affiliation":[{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany."},{"name":"DZD (German Center for Diabetes Research), Site Greifswald, Greifswald, Germany."},{"name":"Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Artati","sequence":"additional","affiliation":[{"name":"Research Unit of Experimental Genetics, Genome Analysis Center, Molecular Endocrinology and Metabolism, Helmholtz Zentrum M\u00fcnchen, Neuherberg, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerzy","family":"Adamski","sequence":"additional","affiliation":[{"name":"Research Unit of Experimental Genetics, Genome Analysis Center, Molecular Endocrinology and Metabolism, Helmholtz Zentrum M\u00fcnchen, Neuherberg, Germany."},{"name":"Lehrstuhl f\u00fcr Experimentelle Genetik, Technische Universit\u00e4t M\u00fcnchen, Freising-Weihenstephan, Germany."},{"name":"DZD 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